Tetrazole and its derivatives are used in the preparation of medicines, agricultural chemicals, foaming agents and automobile inflators. [J. Org. Prep. Proced. Int. 1994, 26, 499; CA 1995, 122, 31359r; Comprehensive Heterocyclic Chemistry II; Storr, R. C. Ed. Elsevier; Oxford, Uk, 1996, vol 4, p621-678].
The preparation of Losartan, a non-peptide angiotensin-II receptro antagonist requires the synthesis of 5-(4'-methyl[1,1'-biphenyl]-2-yl)-1H-tetrazole of the formula 3 below as an intermediate. Basically these approaches consist of the tetrazolyation of 2-cyano-4'-methyl biphenyl of the formula 4 below using tributyl tin azide. [J. Org. Chem. 1991, 36, 2395; U.S. Pat. No. 5,130,439]. ##STR2##
This approach has several drawbacks like longer reaction times and the usage of highly toxic trialkyl tin azide reagents. This process also requires a rigorous purification from stannous compounds in order to obtain the desired biphenyl tetrazole derivatives.
The second approach for the synthesis of biphenyl tetrazole of formula 3 involves the preparation of 5-phenyl-1H-tetrazole with a proper substituent at the ortho position of the phenyl ring such that the biphenyl linkage can be established subsequently. [J. Org. Chem. 1993, 38, 5023]. It has been observed that the ortho substituent suitable for the establishment of the biphenyl linkage is a fluorine atom. 5-(2-fluorophenyl)-1H-tetrazole can be reacted with p-toluene magnesium bromide via Grignard reaction to give 4'methyl 2'-(tetrazolyl)biphenyl in excellent purity. Under the same conditions 5-(2-chlorophenyl)-1H-tetrazole and 5-(2-bromophenyl)-1H-tetrazole failed to provide the desired biphenyl tetrazoles via Grignard reaction because of intramolecular chelation and steric hindrance.
Prior art available to the applicants discloses only one method for the preparation of 5-(2-fluorophenyl)-1H-tetrazole in 69.8% yield [J. Org. Chem. 1993, 38, 5023]. The disclosure in this reference involves the refluxing of 2-fluoro benzonitrile with sodium azide and acetic acid in butanol for two days. The practical utility of this method is suspect due to the in situ generation of hydrozoic acid, which is poisonous and also explosive.
It is therefore essential to develop an efficient method for the preparation of 5-(2-flurophenyl)-1H-tetrazole in order to achieve an efficient process for the preparation of angiotensin--II receptor antagonist Losartan avoiding the drawbacks of the prior art above.